The objective of this research project is to assess the factors responsible for differences in the substrate specificities among cytochrome P-450-dependent microsomal monooxygenase systems from various sources. Present work involves the quantitation of several isozymes of cytochrome P-450 in rabbit liver and lung microsomal preparations and the inductive and repressive effects of various environmental chemicals on the synthesis of these isozymes. Components of the monooxygenase systems are being examined on the basis of catalytic activities as determined in purified and microsomal systems. The enzymes are being quantitated by immunochemical methods. The long range objectives of this research are to: 1) determine the effects of changes in the profiles of isozymes of cytochrome p-450 on overall activity in microsomal preparations and to relate these changes to effects in vivo; 2) to determine differences in the responses of monooxygenase systems from different tissues to exogenous chemicals; and 3) to determine differences in the mechanisms that control the synthesis of isozymes of cytochrome P-450 in rabbit liver and lung.